Data analysis is continuing in a case-control study of risk factors for the acute leukemias in adults in which patients can be classified according to clonal chromosome characteristics, immunologic phenotype, and other biochemical markers, as well as according to more widely available classification systems, to identify risk factors for distinct subgroups and explore possible disease mechanisms. A total of 658 primary leukemia patients who were enrolled in cancer treatment protocols sponsored by Cancer and Leukemia group B, a cooperative cancer study group, and 636 population controls were interviewed regarding exposure to solvents and chemicals, smoking, irradiation, use of potentially toxic medications, and family medical history. In a related ongoing study, we will evaluate cytogenetic abnormalities and ras gene activation for 250 additional patients with acute myelomonocytic leukemia and 90 with myelodysplasia who have completed exposure interviews. Using questionnaire data only, a suggestive increase in leukemia risk was seen for persons living near factories and other sources of environmental pollution. Using questionnaire, histopathologic and cytogenetic data, a smoking effect was found that is strongest for acute myelocytic and myelomonocytic leukemia and for myelocytic leukemia patients with particular cytogenetic abnormalities found in their bone marrow. Using molecular data for a small subset of the patients studied, an association between certain occupational exposures and leukemia was seen that would not have been apparent without the ability to classify patients molecularly; there was a significant association between these exposures and ras-positive leukemia but not ras- negative leukemia.